Severe Septic Patients with Mitochondrial DNA Haplogroup JT Show Higher Survival Rates: A Prospective, Multicenter, Observational Study

Abstract

ObjectiveIn a previous cohort study (n=96), we found an association between mitochondrial (mt) DNA haplogroup JT and increased survival of severe septic patients, after controlling for age and serum lactic acid levels. The aim of this research was to increase the predictive accuracy and to control for more confounder variables in a larger cohort (n=196) of severe septic patients, to confirm whether mtDNA haplogroup JT influences short and medium-term survival in these patients.MethodsWe conducted a prospective, multicenter, observational study in six Spanish Intensive Care Units. We determined 30-day and 6-month survival and mtDNA haplogroup in this second cohort of 196 patients and in the global cohort (first and second cohorts combined) with 292 severe septic patients. Multiple logistic regression and Cox regression analyses were used to test for the association of mtDNA haplogroups JT with survival at 30-days and 6-months, controlling for age, sex, serum interleukin-6 levels and SOFA score.ResultsLogistic and Cox regression analyses showed no differences in 30-day and 6-month survival between patients with mtDNA haplogroup JT and other haplogroups in the first cohort (n=96). In the second cohort (n=196), these analyses showed a trend to higher 30-day and 6-month survival in those with haplogroup JT. In the global cohort (n=292), logistic and Cox regression analyses showed higher 30-day and 6-month survival for haplogroup JT. There were no significant differences between J and T sub-haplogroups in 30-day and 6-month survival.ConclusionsThe global cohort study (first and second cohorts combined), the largest to date reporting on mtDNA haplogroups in septic patients, confirmed that haplogroup JT patients showed increased 30-day and 6-month survival. This finding may be due to single nucleotide polymorphism defining the whole haplogroup JT and not separately for J or T sub-haplogroups.

New Prognostic Biomarkers of Mitochondrial Oxidative Stress in Septic Patients

“…The results of our study (to our knowledge, the largest series providing data on mtDNA and survival in septic patients comprising 96 patients of the first series and 196 patients of the second series with a total of 292 patients) confirmed that haplogroup JT septic patients had increased 30-day and 6-month survival by comparison with non-JT haplogroup patients (93). In the multiple logistic regression analysis, we found that mtDNA haplogroup JT was associated with higher survival at 30-days (OR, 0.38; 95% CI, 0.15 to 0.95; P = 0.04) and 6 months (OR, 0.40; 95% CI, 0.17 to 0.90; P = 0.03) after controlling for age, sex, serum IL-6 levels, and the SOFA score.…”

“…In addition, mtDNA can influence the survival of septic patients, possibly due to the impact of mtDNA on mitochondrial function. The influence of mtDNA on the survival of septic patients has been scarcely studied (90)(91)(92)(93).…”

Mitochondrial DNA sequence variation in multiple sclerosis

“…A previous study identified increased survival in haplogroup JT septic patients and showed that survival may be due to an SNP defining haplogroup JT and not haplogroup J-or Tdefining variants. 17 Another study 18 compared European haplogroup J and H mtDNA using cytoplasmic hybrids or "cybrids" (experimental hybrid cells containing mtDNA from different sources placed in a uniform nuclear DNA background), and haplogroup J cybrids exhibited increased mitochondrial transcription levels and a greater than 2-fold increase in mtDNA copy number compared with haplogroup H cybrids. This is one of the few examples demonstrating functional consequences for variants underlying specific haplogroups.…”

Association Between Mitochondrial DNA Haplogroup and Myelodysplastic Syndromes

“…Several population studies have also evaluated associations between health outcomes and mitochondrial haplogroups. Haplogroup JT has been associated with diverse phenotypes, including improved outcomes following a diagnosis of sepsis (Lorente et al, 2013(Lorente et al, , 2016, reduced risk of diminished ovarian reserve (May-Panloup et al, 2014), and reduced risk of Parkinson disease (Hudson , 2013). In one study of octo/nonagenarians, individuals with haplogroup J had lower systolic blood pressure and glutathione peroxidase activity (Rea et al, 2013).…”